This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human papillomavirus (HPV) is a major cause of sexually transmitted infections (STI) and is the principal cause of cervical cancers worldwide. In much of the Asia-Pacific region, cervical carcinoma ranks first among all cancers in women. Although considerable data are now available about HPV infections in women, almost nothing is known about the natural history of HPV infections among heterosexual men. Lack of such knowledge has impeded progress in the prevention and control of HPV infection in women. The objective of this research project is to determine the molecular epidemiology and natural history of HPV infection in heterosexual men. Our central hypothesis is that, as in women, HPV is a common (high prevalence and incidence) but usually transient infection in heterosexual men. We further posit that young age and low HPV viral level will be associated with transient infections, while older age and high HPV viral load will predict viral persistence. The proposed study will test our hypotheses by pursuing the following specific aims: 1. Determine the prevalence and incidence of genital HPV infection in heterosexual adult men. 2. Determine the relative transience and persistence of genital HPV infection in heterosexual adult men. 3. Determine the viral and host factors associated with prevalent, incident, transient, and persistent genital HPV infection in heterosexual adult men. A cohort of 640 adult men will be followed longitudinally at four-month intervals for 24 months. Exfoliated cells from the genitalia (penile shaft, glans/coronal sulcus, urethra) will be analyzed for HPV DNA by PCR. Infections will be characterized by HPV genoyping and variant analysis. Also, we will evaluate information on sexual history and practices, contraceptive use, history of STI, tobacco and alcohol use, and sociodemographic characteristics. The proposed project is innovative, because it addresses a major gap in current knowledge. Our expectations are that we will have a better understanding about the natural history of HPV in men. This newfound knowledge will have a significant impact on improving future prevention strategies for HPV infection.